Ezetimibe Component Of These Drugs Is Associated With Liver Failure, Acute Pancreatitis, Rhabdomyolysis, and Thrombocytopenia

(Posted by Tom Lamb at DrugInjuryWatch.com)

Ezetimibe is used alone (i.e., Zetia) or in combination with other antilipemic agents such as a statin or fenofibrate.  In some instances, ezetimibe is in fixed combination with simvastatin (i.e., Vytorin).

Zetia and Vytorin are prescribed as an adjunct to dietary therapy in the treatment of primary hypercholesterolemia and mixed dyslipidemia, as well as homozygous familial hypercholesterolemia and/or homozygous familial sitosterolemia.  As is relatively well-known by now, however, the efficacy of Zetia and Vytorin was called into question when the results of the ENHANCE clinical study were finally released in January 2008 by Merck and Schering-Plough.

For some recent developments concerning the ENHANCE study controversy as well as the related issue of whether Zetia and Vytorin are effective treatments, we refer you to these two leading sources of information:

"Early Communication about an Ongoing Data Review for Ezetimibe/Simvastatin (marketed as Vytorin), Ezetimibe (marketed as Zetia), and Simvastatin (marketed as Zocor)", which was issued by the FDA on January 25, 2008; and,

"Merck and Schering-Plough Respond To Issues Raised About ENHANCE Clinical Trial", a January 25, 2008 press release that these two drug companies managed to get out in advance of the FDA alerting the public about its Early Communication item concerning Zetia and Vytorin later that day.  This press release includes a link to an an ENHANCE Chronology (PDF format) prepared by Merck and/or Schering-Plough which is seemingly intended to reinforce the claims made in their press release.

Moving to the drug-safety aspect, there have been reports of Zetia and Vytorin causing some serious side effects, such as:

• drug-induced hepatitis;
• liver failure;
• acute pancreatitis;
• rhabdomyolysis; and,
• thrombocytopenia.

On February 6, 2008 we received The Annals Online Articles Ahead of Print Alert about a new article concerning a Vytorin adverse drug reaction report that was published online by The Annals of Pharmacotherapy before this article’s scheduled publication in its March edition.  The Abstract for "Ezetimibe-Associated Immune Thrombocytopenia", this March 2008 medical journal article about Vytorin, provides these basic facts:

• OBJECTIVE: To describe a case of immune thrombocytopenia associated with treatment with ezetimibe, a cholesterol absorption inhibitor.
• CASE SUMMARY: A 72-year-old man presented with severe thrombocytopenia (platelets 3 x 103/µL) and "wet purpura" 4 weeks after being started on daily therapy using a combination of ezetimibe 10 mg/simvastatin 20 mg. Platelet counts normalized after administration of ezetimibe/ simvastatin was stopped. Nine months later, the patient was restarted on simvastatin because of uncorrected dyslipidemia. Platelet counts remained within the normal range following that rechallenge.
• DISCUSSION: Registry data revealed the possibility of ezetimibe-induced thrombocytopenia, but, as of December 3, 2007, no other case reports on this interaction had been published. This case illustrates the probable occurrence of ezetimibe-induced thrombocytopenia. Platelet counts dropped significantly when ezetimibe therapy was initiated, then resolved upon discontinuation of therapy. Other causes of thrombocytopenia were ruled out, and rechallenge with simvastatin further supports the presence of a causal relationship between thrombocytopenia and ezetimibe….
• CONCLUSIONS: Ezetimibe-associated thrombocytopenia cannot be ruled out in the patient reported here. Clinicians should be aware of this adverse event.

We will continue to watch for drug-injury reports concerning Vytorin as well as Zetia in the medical journals, and letting you know what we find, here.